A phase IIA study of the histone-deacetylase inhibitor ITF2357 in patients with JAK-2 V617F positive chronic myeloproliferative diseases - ND

• Conditions: chronic myeloproliferative diseases; MedDRA version: 6.1Level: HLTClassification code 10028578

• Registration Number: EUCTR2007-004480-21-IT
• Lead Sponsor: ITALFARMACO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-01-10
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Signed Informed Consent Form
Male or female, age ≥ 18 years
Confirmed diagnosis of PV/ET/MF according to the revised WHO criteria
JAK-2 V617F positivity
In need of cytoreductive therapy when hydroxyurea is not indicated (e.g. young patients) or when refractoriness to the drug is documented
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Active bacterial or fungal infection requiring antimicrobial treatment on Day 1
Patients of childbearing potential without a negative pregnancy test prior to initiation of the study drug
Pregnancy or lactation
A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett?s correction formula ? see appendix G for the formula)
The use of concomitant medications that prolong the QT/QTc interval (see appendix F for full list)
Concomitant acute coronary syndromes; uncontrolled hypertension
New York Heart Association (NYHA) Grade II or greater congestive heart failure
History of any cardiac arrhythmia requiring medication (irrespective of its severity)
A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
Active EBV infection (i.e. positive serology IgM)
Known HIV infection
Active hepatitis B and/or C infection
History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications
ECOG performance status 3 or greater
Platelets count <100x109/L within 14 days before enrolment
Absolute neutrophil count <1.2x109/L within 14 days before enrolment
Percentage of blast cells in peripheral blood >10% within 14 days before enrolment
Serum creatinine >2xULN
Total serum bilirubin >1.5xULN
Serum AST/ALT > 3xULN
Interferon alpha within 14 days before enrolment
Hydroxyurea within 14 days before enrolment
Anagrelide within 7 days before enrolment
Any other investigational drug within 28 days before enrolment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate efficacy and safety of ITF 2357 in the treatment of patients with JAK2 V617F positive myeloproliferative diseases (PV, ET, MF). Efficacy will be evaluated by ad hoc haematological and clinical criteria for PV and ET, and by internationally established response criteria for MF. Safety will be evaluated by number of subjects experiencing an AE, type, frequency, severity, timing and relatedness of AEs (including changes in vital signs and clinical laboratory results;Secondary Objective: to evaluate the JAK2 mutated allele burden by quantitative RT PCR;Primary end point(s): The number of Objective Responses (OR)<br>The number of subjects experiencing an adverse event